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BACKGROUND: Clozapine is the most effective antipsychotic for treatment-resistant psychosis. However, clozapine is underutilised in part because of potential agranulocytosis. Accumulating evidence indicates that below-threshold haematological readings in isolation are not diagnostic of life-threatening clozapine-induced agranulocytosis (CIA). AIMS: To examine the prevalence and timing of CIA using different diagnostic criteria and to explore demographic differences of CIA in patients registered on the UK Central Non-Rechallenge Database (CNRD). METHOD: We analysed data of all patients registered on the UK Clozaril® Patient Monitoring Service Central Non-Rechallenge Database (at least one absolute neutrophil count (ANC) < 1.5 × 109/L and/or white blood cell count < 3.0 × 109/L) between May 2000 and February 2021. We calculated prevalence rates of agranulocytosis using threshold-based and pattern-based criteria, stratified by demographic factors (gender, age and ethnicity). Differences in epidemiology based on rechallenge status and clozapine indication were explored. The proportion of patients who recorded agranulocytosis from a normal ANC was explored. RESULTS: Of the 3029 patients registered on the CNRD with 283 726 blood measurements, 593 (19.6%) were determined to have threshold-based agranulocytosis and 348 (11.4%) pattern-based agranulocytosis. In the total sample (75 533), the prevalence of threshold-based agranulocytosis and pattern-based agranulocytosis was 0.8% and 0.5%, respectively. The median time to threshold-based agranulocytosis was 32 weeks (IQR 184) and 15 (IQR 170) weeks for pattern-based agranulocytosis. Among age groups, the prevalence of pattern-based agranulocytosis and threshold-based agranulocytosis was highest in the >48 age group. Prevalence rates were greatest for White (18%) and male individuals (13%), and lowest for Black individuals (0.1%). The proportion of people who were determined to have pattern-based agranulocytosis without passing through neutropenia was 70%. CONCLUSIONS: Threshold-based definition of agranulocytosis may over-diagnose CIA. Monitoring schemes should take into consideration neutrophil patterns to correctly identify clinically relevant CIA. In marked contrast to previous studies, CIA occurred least in Black individuals and most in White individuals.
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BACKGROUND: Clozapine is the only recommended antipsychotic medication for individuals diagnosed with treatment-resistant schizophrenia. Unfortunately, its wider use is hindered by several possible adverse effects, some of which are rare but potentially life threatening. As such, there is a growing interest in studying clozapine use and safety in routinely collected healthcare data. However, previous attempts to characterise clozapine treatment have had low accuracy. AIM: To develop a methodology for identifying clozapine treatment dates by combining several data sources and implement this on a large clinical database. METHODS: Non-identifiable electronic health records from a large mental health provider in London and a linked database from a national clozapine blood monitoring service were used to obtain information regarding patients' clozapine treatment status, blood tests and pharmacy dispensing records. A rule-based algorithm was developed to determine the dates of starting and stopping treatment based on these data, and more than 10% of the outcomes were validated by manual review of de-identified case note text. RESULTS: A total of 3,212 possible clozapine treatment periods were identified, of which 425 (13.2%) were excluded due to insufficient data to verify clozapine administration. Of the 2,787 treatments remaining, 1,902 (68.2%) had an identified start-date. On evaluation, the algorithm identified treatments with 96.4% accuracy; start dates were 96.2% accurate within 15 days, and end dates were 85.1% accurate within 30 days. CONCLUSIONS: The algorithm produced a reliable database of clozapine treatment periods. Beyond underpinning future observational clozapine studies, we envisage it will facilitate similar implementations on additional large clinical databases worldwide.
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Algoritmos , Antipsicóticos , Clozapina , Registros Electrónicos de Salud , Clozapina/uso terapéutico , Clozapina/efectos adversos , Humanos , Registros Electrónicos de Salud/estadística & datos numéricos , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Adulto , Masculino , Esquizofrenia Resistente al Tratamiento/tratamiento farmacológico , Femenino , Londres , Bases de Datos Factuales , Persona de Mediana EdadRESUMEN
BACKGROUND: To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust. AIMS: To investigate the impact of this temporary policy change on clinical and safety outcomes. METHOD: All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined. RESULTS: Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02-28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection. CONCLUSIONS: There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.
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Antipsicóticos , COVID-19 , Clozapina , Neutropenia , Humanos , Clozapina/efectos adversos , Antipsicóticos/efectos adversos , Estudios de Cohortes , Medicina Estatal , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Neutropenia/tratamiento farmacológicoRESUMEN
BACKGROUND: Up to 30% of patients with a diagnosis of treatment-resistant psychosis remain symptomatic despite an optimal trial with the gold standard treatment, clozapine. Emerging evidence suggests the clinical utility of long-acting injections (LAI) in such clinical scenarios. In this study, we aimed to describe clozapine augmentation with LAIs in an inner London hospital and explore the literature on the clinical effectiveness of this treatment modality. METHODS: Patients prescribed clozapine, who were commenced on a LAI between 2007 and 2023 by the United Kingdom's largest mental health trust, were identified from electronic patient records. First, routine clinical data were used to describe the use, effectiveness, and safety of this augmentation strategy. Second, we conducted a literature search up to 1st June 2023 to identify published studies describing clinical outcomes after clozapine augmentation with a LAI. Clinical outcomes were collated and presented in a table, including hospitalisation rates and quantitative clinical assessments using validated scales. RESULTS: Of the 1248 patients prescribed clozapine in SLaM, three patients (0.2%) received augmentation with the following LAIs: olanzapine embonate, paliperidone palmitate and pipotiazine palmitate. This treatment strategy was clinically effective and generally well tolerated in all three cases. Twelve published studies between 2010 and 2022 were included in the review. Eight distinct LAIs were reported (4 first and 4 second generation antipsychotics), with risperidone and paliperidone most widely studied. All the identified studies were observational including mirror-image studies, case series and case reports. Duration of follow up varied from 3 months to 3 years. There was evidence that the use of LAIs with clozapine can significantly reduce clinical symptoms, hospitalisation rates and bed days. No serious adverse effects were reported. CONCLUSION: This preliminary evidence suggests clinical utility of LAIs in alleviating residual symptoms and subsequently reducing hospitalisation rates in patients optimised on clozapine treatment. The current study warrants further investigations including a randomised controlled study to establish the clinical efficacy, tolerability, and place in therapy of this treatment modality.
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Antipsicóticos , Clozapina , Esquizofrenia , Humanos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Clozapina/efectos adversos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inducido químicamente , Risperidona/uso terapéutico , Palmitato de Paliperidona/uso terapéutico , Preparaciones de Acción Retardada/uso terapéuticoRESUMEN
BACKGROUND: Clozapine is the treatment of choice in refractory psychosis. In most countries, clozapine must be stopped indefinitely if white blood cells fall below a defined threshold during routine monitoring. Despite evidence of severe adverse consequences of clozapine discontinuation, published accounts on the lived experiences and perspectives of patients and carers are scarce. METHOD: We completed semi-structured interviews with patients (n = 4) and family carers (n = 4) on experiences of clozapine cessation following suspected drug-induced neutropenia. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: The two overarching themes comprised:(i) stress of clozapine below threshold neutrophil results and (ii) patient and carer priorities. CONCLUSIONS: There is a suggested need for evidence-based pharmacological and psychological approaches to support patients and carers after clozapine cessation. Such approaches will minimise the potentially negative physical and emotional sequela in the aftermath of a below threshold neutrophil result and reduce the likelihood of experiencing additional health and social inequalities after clozapine discontinuation.
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Antipsicóticos , Clozapina , Neutropenia , Trastornos Psicóticos , Humanos , Clozapina/efectos adversos , Cuidadores/psicología , Neutropenia/inducido químicamente , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/psicología , Registros , Antipsicóticos/efectos adversosRESUMEN
OBJECTIVE: The objective of the study is to explore the long-term effectiveness and tolerability of metoclopramide in the treatment of CIH. METHOD: This study is a retrospective, observational cohort study of patients prescribed metoclopramide for CIH at the South London & Maudsley (SLaM) NHS Foundation Trust. RESULTS: Of the 96 patients identified, 14 patients were eligible for inclusion in our study. Five patients continued treatment with a mean duration of 27 months (SD = 17.8), and one patient continued until transfer with a duration of 3 months. Eight patients discontinued treatment after a mean duration of 8 months. CONCLUSION: Metoclopramide may be an effective and tolerated drug in CIH, but more data is required to establish its place in the pharmacotherapy of this condition.
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Antipsicóticos , Clozapina , Esquizofrenia , Sialorrea , Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Humanos , Metoclopramida/efectos adversos , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológico , Sialorrea/inducido químicamente , Sialorrea/tratamiento farmacológicoRESUMEN
BACKGROUND: Clozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences. AIMS: To examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects. METHOD: A retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined. RESULTS: Of 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation. CONCLUSIONS: Suspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The 'critical period' for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.
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Antipsicóticos , Clozapina , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Miocarditis , Antipsicóticos/efectos adversos , Biomarcadores , Clozapina/efectos adversos , Electrónica , Humanos , Incidencia , Miocarditis/inducido químicamente , Miocarditis/diagnóstico , Miocarditis/epidemiología , Estudios Retrospectivos , Taquicardia/inducido químicamente , TroponinaRESUMEN
BACKGROUND: Clozapine is the only licensed treatment for treatment refractory schizophrenia. Despite this, it remains grossly underused relative to the prevalence of refractory schizophrenia. The extent of underuse and the degree of regional variation in prescribing in the United Kingdom is unknown. It is also unclear, how the UK compares with other European countries in rates of clozapine prescribing. METHODS: We obtained data relating to all clozapine prescribing in the UK from the relevant clozapine registries. We examined regional variation in clozapine use across England, corrected for the known prevalence of severe mental illness (SMI). We also compared the UK rate of clozapine use per 100,000 population to that described in other European countries. FINDINGS: There is substantial variation in clozapine prescribing across different regions of England and only about a third of potentially eligible patients were prescribed the drug in the UK. Clozapine prescribing rate in the UK was lower than in several European countries. INTERPRETATION: There is clear regional inequity in access to the most effective treatment in refractory schizophrenia in England. Strategies to increase clozapine use, by overcoming both real and perceived barriers, are urgently necessary to reduce treatment inequity for patients with refractory schizophrenia.
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Antipsicóticos , Clozapina , Esquizofrenia , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Humanos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/epidemiología , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Benign ethnic neutropenia (BEN) is the most common cause of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent. This phenotype is broadly defined by an absolute neutrophil counts (ANC) below 1.8 × 109 cells/L in the absence of other causes, without an increased risk of infection. BEN has been implicated as a potential source of disparity in patients treated with clozapine, the antipsychotic of choice in treatment-resistant schizophrenia. Our main objective was to examine the current level of BEN recognition in a cohort of patients treated with clozapine and the potential impact of unidentified BEN on the initiation and maintenance of clozapine treatment. METHODS: This was an observational, retrospective analysis of patients registered with clozapine haematological monitoring systems in two large mental health trusts, chosen because they serve an ethnically diverse population. The first objective was to establish certified BEN prevalence in current users of clozapine. The second objective was to explore the stage of treatment at which BEN was identified. The third objective was to evaluate the extent of unrecognised BEN in patients registered on the Central Non-Rechallenge Database (CNRD), a database for patients whose haematological parameters fall below set thresholds when receiving clozapine treatment, meaning they cannot ordinarily be prescribed clozapine again. RESULTS: The study population comprised of 2020 patients on the clozapine register. 111 patients were monitored under BEN criteria. BEN was mostly identified after a below threshold haematological result or clozapine rechallenge (68%) compared to at clozapine initiation (32%). Eight of the 18 (42%) black patients registered on the CNRD were classified as BEN after assessment by a haematologist. Of these 8 patients, none would have met CNRD criteria again if monitored with BEN criteria at clozapine initiation. CONCLUSIONS: Current evidence suggests that BEN remains an uncommonly recognised haematological phenotype. Improved timely identification of BEN will reduce unnecessary interruption or discontinuation of clozapine treatment. Our results suggest consideration should also be given to determining BEN status prior to initiating clozapine. Moreover, adoption of current FDA BEN monitoring criteria in the UK may further reduce clozapine discontinuation due to perceived neutropenia as drug toxicity, particularly in treatment-refractory schizophrenia patients.
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Antipsicóticos , Clozapina , Neutropenia , Antipsicóticos/uso terapéutico , Clozapina/efectos adversos , Hospitales , Humanos , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Prevalencia , Estudios Retrospectivos , Medicina EstatalRESUMEN
BACKGROUND: Clozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored. AIMS: This was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period. METHOD: Successful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication. RESULTS: Among 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14-1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11-1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling. CONCLUSIONS: Intramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.
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Antipsicóticos , Clozapina , Trastornos Psicóticos , Esquizofrenia , Cuidados Posteriores , Antipsicóticos/uso terapéutico , Humanos , Alta del Paciente , Prescripciones , Trastornos Psicóticos/tratamiento farmacológico , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológicoRESUMEN
BACKGROUND AND OBJECTIVE: Clozapine is the drug of choice for treatment-resistant schizophrenia. The primary objective of this study was to compare plasma clozapine and N-desmethylclozapine levels in patients switched between 2 liquid formulations [Denzapine suspension and clozapine oral solution (St George's ZTAS)]. Secondary objectives included comparison of safety, tolerability, and patient acceptability. METHODS: This was a noninterventional, observational, prospective follow-up of patients consecutively switched between formulations of clozapine liquid in a large inner-city NHS mental health trust. The authors also performed retrospective analysis of outcomes from patient case notes. RESULTS: The authors identified 43 patients receiving Denzapine suspension in the trust. Data were available for 43 patients switched from Denzapine to clozapine oral solution (St George's ZTAS), among whom, 15 (32%) were excluded from the analysis. Of the 28 patients for whom data were available, the 90% confidence interval for the ratio of mean values for corrected Cmin 91.5 (85.2%-98.4%) and uncorrected Cmin 91.2 (84.4%-98.6%) were within the guideline range of bioequivalence (80%-125%). Safety and tolerability profiles were comparable between the 2 formulations (P = 0.10). Patient acceptability was also similar between the brands in most domains. However, there was a taste preference for Denzapine suspension. CONCLUSIONS: No significant difference in clozapine plasma levels was observed after switching from Denzapine suspension to a recently introduced clozapine solution. This study also highlights the significance of medicinal characteristics such as taste for patient acceptability and compliance.
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Antipsicóticos/sangre , Antipsicóticos/uso terapéutico , Clozapina/análogos & derivados , Clozapina/sangre , Clozapina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Antipsicóticos/efectos adversos , Antipsicóticos/farmacocinética , Clozapina/efectos adversos , Clozapina/farmacocinética , Monitoreo de Drogas/métodos , Femenino , Humanos , Masculino , Estudios Prospectivos , Equivalencia TerapéuticaRESUMEN
Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of this article is to provide an update on current knowledge relating to: the pattern and incidence of severe blood dyscrasias; the effectiveness of current monitoring regimes in reducing harm; the mechanisms of and the distinctions between clozapine-induced neutropenia and agranulocytosis; benign ethnic neutropenia; and changes to the monitoring thresholds in the USA and other international variations. These all have implications for the practical use of clozapine; specifically, how barriers to initiating, maintaining and restarting clozapine can be understood and in many cases overcome, especially for patients from minority groups, potentially with simpler approaches than the use of lithium or G-CSF.
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Clozapine is the most effective medication for treatment-resistant psychosis, but evidence points to substantial underuse, especially within early intervention psychosis (EIP) services. We explored clinicians' views on perceived barriers and facilitators to offering patients clozapine within EIP services. A cross-sectional survey was distributed electronically to clinicians practising in EIP services across England. A mixed methods approach was used to assess barriers to clozapine, and attitudes and opinions concerning clozapine underutilisation. Based on the barriers identified in the literature, clinicians were asked to rate each one (scale:1-7) based on importance, with a higher score indicating higher importance. Clinicians were also asked open-ended questions on barriers to clozapine and how access can be improved in EIP services. Quantitative data were analysed using descriptive and inferential statistics, and qualitative responses were analysed thematically. One hundred and nineteen EIP clinicians from 35 services in England completed the survey. In total, 37% (n = 45) of clinicians perceived that clozapine was under-prescribed in their EIP service. The most important barrier to utilising clozapine were patient concerns with side effects, followed by monitoring requirements and clinician concerns with side effects. Thematic analysis identified 17 perceived barriers, which were grouped into three major themes: administrative (5 subthemes), clinician-related (6 subthemes), and patient-related (6 subthemes). Perceived facilitators to improving clozapine use were greater training, improved resources, and optimised monitoring. The main barriers to clozapine in EIP services, as identified by clinicians, are patient concerns regarding side effects and monitoring requirements. Identified facilitators for improved clozapine use include clinician training, improved resources, guidelines, and point-of-care testing.
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Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respond to standard antipsychotics could be fast-tracked to clozapine. Using proton magnetic resonance spectroscopy (1H-MRS), we examined the ability of glutamate and Glx (glutamate plus glutamine) in the anterior cingulate cortex (ACC) and caudate to predict response to antipsychotic treatment. A total of 89 minimally medicated patients with FEP not meeting symptomatic criteria for remission were recruited across two study sites. 1H-MRS and clinical data were acquired at baseline, 2 and 6 weeks. Response was defined as >20% reduction in Positive and Negative Syndrome Scale (PANSS) Total score from baseline to 6 weeks. In the ACC, baseline glutamate and Glx were higher in Non-Responders and significantly predicted response (P < 0.02; n = 42). Overall accuracy was greatest for ACC Glx (69%) and increased to 75% when symptom severity at baseline was included in the model. Glutamate metabolites in the caudate were not associated with response, and there was no significant change in glutamate metabolites over time in either region. These results add to the evidence linking elevations in ACC glutamate metabolites to a poor antipsychotic response. They indicate that glutamate may have utility in predicting response during early treatment of first episode psychosis. Improvements in accuracy may be made by combining glutamate measures with other response biomarkers.
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Antipsicóticos , Trastornos Psicóticos , Esquizofrenia , Humanos , Ácido Glutámico/metabolismo , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/metabolismo , Esquizofrenia/tratamiento farmacológico , Espectroscopía de Protones por Resonancia Magnética/métodosRESUMEN
Background: Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia (TRS), however, it remains widely under-utilized in clinical practice. To date, relatively little attention has been given to patients' experience of clozapine. By synthesizing the existing literature, we sought to determine the experiences of patients with TRS treated with clozapine. Methods: A systematic review was conducted on Embase, Medline, PsychInfo, and PubMed databases for studies from 1956 to 2021. English language studies and those based on adult patients prescribed clozapine for TRS were included. Results: Thirteen studies were included with a total of 1487 patients and a narrative synthesis was performed. Overall, most patients reported positive experiences of clozapine, with generally high levels of satisfaction, alongside symptom improvement and preference over previous medications. Negative experiences of clozapine were less common, but when mentioned, focused on blood tests and common side effects, including hypersalivation and weight gain. Conclusions: This is the first systematic review exploring patients' subjective experiences of clozapine for TRS. Findings suggest that patients generally have a favorable experience when being treated with clozapine. However, conclusions are limited by the risk of bias, particularly survivorship bias. High-quality longitudinal studies exploring patients' experiences of clozapine are indicated for the future.
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Only about 50% of patients with treatment-resistant schizophrenia respond to clozapine, and many more patients continue to experience ongoing and prominent negative symptoms. These negative symptoms, for which there are limited pharmacological options, may represent the greatest barrier to functional recovery. Cariprazine is a novel antipsychotic drug that is a partial agonist at dopamine D2 and D3 receptors with preferential binding to the D3 receptor, antagonism of 5HT2B receptors, and partial agonism at 5HT1A receptors. Cariprazine is currently licenced for the treatment of schizophrenia in Europe and the United States and has also been approved for bipolar disorder in the United States. There is a limited body of evidence to suggest clinical effectiveness as an augmentation strategy for negative symptoms in those treated with clozapine. In this case series, we present five cases of successful treatment of negative symptoms by clozapine combined with cariprazine in treatment-resistant psychosis.
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BACKGROUND: To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI). METHOD: A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services. RESULTS: The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; p = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15-15.76, p = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related. CONCLUSION: Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.